Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

in Advanced science (Weinheim, Baden-Wurttemberg, Germany) by Meng Huang, Shao Xu, Yuzhe Li, Li Shang, Xiudan Zhan, Chaoyin Qin, Jun Su, Zijin Zhao, Yi He, Lina Qin, Wei Zhao, Wenyong Long, Qing Liu

TLDR

  • The study identifies a unique cell type in high-grade meningiomas that promotes the growth and spread of the tumor. The study establishes a new way to study this cell type and identifies a potential treatment for the disease. The study suggests that this treatment could be personalized to each patient based on their specific tumor characteristics. The study is labeled as string and called

Abstract

High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

Overview

  • The study aims to identify the initiating cell subpopulation in high-grade meningiomas and its role in the progression and recurrence of the disease. The methodology used includes single-cell RNA sequencing (scRNA-Seq) and patient-derived meningioma organoid (MO) models. The primary objective is to establish a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called
  • The study focuses on high-grade meningiomas, which have an unsatisfactory outcome despite surgery and postoperative radiotherapy. The hypothesis being tested is that the factors driving their malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. The methodology used includes scRNA-Seq to identify a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas. The primary objective is to establish a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called
  • The study aims to identify the initiating cell subpopulation in high-grade meningiomas and its role in the progression and recurrence of the disease. The methodology used includes scRNA-Seq and patient-derived meningioma organoid (MO) models. The primary objective is to establish a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called

Comparative Analysis & Findings

  • The study identifies a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas that modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. The key findings of the study are that SULT1E1 plays a crucial role in the progression and recurrence of high-grade meningiomas and that targeting this subpopulation could be a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called
  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas that modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. The key findings of the study are that SULT1E1 plays a crucial role in the progression and recurrence of high-grade meningiomas and that targeting this subpopulation could be a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called
  • The study discusses the key findings of the study and how they relate to the initial hypothesis. The study identifies a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas that modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. The key findings of the study are that SULT1E1 plays a crucial role in the progression and recurrence of high-grade meningiomas and that targeting this subpopulation could be a novel therapeutic target for refractory high-grade meningioma. The study is labeled as string and called

Implications and Future Directions

  • The study's findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma. The study identifies a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas that modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. The study establishes a novel patient-derived meningioma organoid (MO) model to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. The study's findings suggest that targeting SULT1E1 could be a novel therapeutic target for refractory high-grade meningioma. The study identifies several limitations, such as the small sample size and the need for further validation in animal models and clinical trials. The study suggests several future research directions, such as investigating the role of SULT1E1 in other brain tumors, exploring the combination of SRT1720 with other therapies, and developing personalized treatments based on the patient's SULT1E1 profile. The study is labeled as string and called
  • The study's findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma. The study identifies a unique initiating cell subpopulation (SULT1E1) in high-grade meningiomas that modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. The study establishes a novel patient-derived meningioma organoid (MO) model to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. The study's findings suggest that targeting SULT1E1 could be a novel therapeutic target for refractory high-grade meningioma. The study identifies several limitations, such as the small sample size and the need for further validation in animal models and clinical trials. The study suggests several future research directions, such as investigating the role of SULT1E1 in other brain tumors, exploring the combination of SRT1720 with other therapies, and developing personalized treatments based on the patient's SULT1E1 profile. The study is labeled as string and called
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